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Transcranial Doppler is a widely used noninvasive technique for assessing cerebral artery blood flow. All previous high altitude studies assessing cerebral blood flow (CBF) in the field that have used Doppler to measure arterial blood velocity have assumed vessel diameter to not alter. Here, we report two studies that demonstrate this is not the case. First, we report the highest recorded study of CBF (7,950 m on Everest) and demonstrate that above 5,300 m, middle cerebral artery (MCA) diameter increases (n=24 at 5,300 m, 14 at 6,400 m, and 5 at 7,950 m). Mean MCA diameter at sea level was 5.30 mm, at 5,300 m was 5.23 mm, at 6,400 m was 6.66 mm, and at 7,950 m was 9.34 mm (P<0.001 for change between 5,300 and 7,950 m). The dilatation at 7,950 m reversed with oxygen. Second, we confirm this dilatation by demonstrating the same effect (and correlating it with ultrasound) during hypoxia (FiO2=12% for 3 hours) in a 3-T magnetic resonance imaging study at sea level (n=7). From these results, we conclude that it cannot be assumed that cerebral artery diameter is constant, especially during alterations of inspired oxygen partial pressure, and that transcranial 2D ultrasound is a technique that can be used at the bedside or in the remote setting to assess MCA caliber.

BackgroundThe physiological responses to hypoxaemia and cellular hypoxia are poorly understood, and inter-individual differences in performance at altitude and outcome in critical illness remain unexplained. We propose a model for exploring adaptation to hypoxia in the critically ill: the study of healthy humans, progressively exposed to environmental hypobaric hypoxia (EHH). The aim of this study was to describe the spectrum of adaptive responses in humans exposed to graded EHH and identify factors (physiological and genetic) associated with inter-individual variation in these responses.MethodsDesignObservational cohort study of progressive incremental exposure to EHH.SettingUniversity human physiology laboratory in London, UK (75 m) and 7 field laboratories in Nepal at 1300 m, 3500 m, 4250 m, 5300 m, 6400 m, 7950 m and 8400 m.Participants198 healthy volunteers and 24 investigators trekking to Everest Base Camp (EBC) (5300 m). A subgroup of 14 investigators studied at altitudes up to 8400 m on Everest.Main outcome measuresExercise capacity, exercise efficiency and economy, brain and muscle Near Infrared Spectroscopy, plasma biomarkers (including markers of inflammation), allele frequencies of known or suspected hypoxia responsive genes, spirometry, neurocognitive testing, retinal imaging, pupilometry. In nested subgroups: microcirculatory imaging, muscle biopsies with proteomic and transcriptomic tissue analysis, continuous cardiac output measurement, arterial blood gas measurement, trans-cranial Doppler, gastrointestinal tonometry, thromboelastography and ocular saccadometry.ResultsOf 198 healthy volunteers leaving Kathmandu, 190 reached EBC (5300 m). All 24 investigators reached EBC. The completion rate for planned testing was more than 99% in the investigator group and more than 95% in the trekkers. Unique measurements were safely performed at extreme altitude, including the highest (altitude) field measurements of exercise capacity, cerebral blood flow velocity and microvascular blood flow at 7950 m and arterial blood gas measurement at 8400 m.ConclusionsThis study demonstrates the feasibility and safety of conducting a large healthy volunteer cohort study of human adaptation to hypoxia in this difficult environment. Systematic measurements of a large set of variables were achieved in 222 subjects and at altitudes up to 8400 m. The resulting dataset is a unique resource for the study of genotype:phenotype interactions in relation to hypoxic adaptation.

Object There is increasing evidence that simulation provides high-quality, time-effective training in an era of resident duty-hour restrictions. Simulation may also permit trainees to acquire key skills in a safe environment, important in a specialty such as neurosurgery, where technical error can result in devastating consequences. The authors systematically reviewed the application of simulation within neurosurgical training and explored the state of the art in simulation within this specialty. To their knowledge this is the first systematic review published on this topic to date. Methods The authors searched the Ovid MEDLINE, Embase, and PsycINFO databases and identified 4101 articles; 195 abstracts were screened by 2 authors for inclusion. The authors reviewed data on study population, study design and setting, outcome measures, key findings, and limitations. Results Twenty-eight articles formed the basis of this systematic review. Several different simulators are at the neurosurgeon's disposal, including those for ventriculostomy, neuroendoscopic procedures, and spinal surgery, with evidence for improved performance in a range of procedures. Feedback from participants has generally been favorable. However, study quality was found to be poor overall, with many studies hampered by nonrandomized design, presenting normal rather than abnormal anatomy, lack of control groups and long-term follow-up, poor study reporting, lack of evidence of improved simulator performance translating into clinical benefit, and poor reliability and validity evidence. The mean Medical Education Research Study Quality Instrument score of included studies was 9.21 ± 1.95 (± SD) out of a possible score of 18. Conclusions The authors demonstrate qualitative and quantitative benefits of a range of neurosurgical simulators but find significant shortfalls in methodology and design. Future studies should seek to improve study design and reporting, and provide long-term follow-up data on simulated and ideally patient outcomes.

Arterial hypoxemia is associated with cerebral and retinal venous distension, whose magnitude correlates with HAH burden. Restriction in cerebral venous outflow is associated with retinal distension and HAH. Limitations in cerebral venous efferent flow may predispose to headache when hypoxia-related increases in cerebral arterial flow occur.

Syndromes thought to have cerebral venous hypertension as their core, such as idiopathic intracranial hypertension and jugular foramen outlet obstruction, classically result in headaches. Do they provide an insight into the cause of the headache that commonly occurs at altitude? The classic theory of the pathogenesis of high altitude headache has been that it results from increased intracranial pressure (ICP) secondary to hypoxemia in people who have less compliant intracranial volumes (Roach and Hackett, 2001). However, there does not appear to be a correlation between the headache of acute mountain sickness (AMS) and the presence of cerebral edema (Bailey et al, 2006; Wilson et al, 2009). Research has concentrated on arterial perfusion to the brain in hypoxia, but there has been little study of venous drainage. Hypoxia results in markedly increased cerebral blood flow; however, if it has been considered at all, venous outflow has to date been assumed to be of little consequence. Retinal venous distension and the increased venous blood demonstrated by near infra-red spectroscopy and more recently by MRI imply that, in hypoxia, a relative venous insufficiency may exist. Similarly, there is increasing evidence that manifestations of the fluid shift during microgravity is of similar nature to idiopathic intracranial hypertension, which is thought to be primarily a venous insufficiency condition. The unique anthropomorphic adaptations of large brained biped humans with cerebral venous systems that have to cope with large changes in hydrostatic pressure may predispose us to conditions of inflow/outflow mismatch. In addition, slight increases in central venous pressures (e.g., from hypoxia-induced pulmonary vasoconstriction) may further compromise venous outflow at altitude. A better understanding of cerebral venous physiology may enlighten us with regards the pathogenesis of headaches currently considered idiopathic. It may also enable us to trigger headaches for study and hence enable us to develop new treatment strategies.

Age has been identified as an independent risk factor for poor outcome following head injury in the elderly, and postulated reasons for this include nature, nurture, and variations in management. Do elderly head injuries do worse because of a self-fulfilling prophecy of poorer management? The aim of this study was to review the management of patients with cerebral contusions according to age to identify any trends. We retrospectively reviewed prospectively collected national data on cerebral contusion admissions between March 14, 1988, and May 4, 2012, to UK hospitals held in the Trauma Audit and Research Network database. Patients were included in the study if they had cerebral contusion(s) with an abbreviated injury score (AIS) of 3 or more; no other head injury with a AIS score of 4 or more, or no injury in any other body region with AIS score of 3 or more, and known outcome data. In total, 4387 patients met the inclusion criteria. Mortality was found to increase with increasing age (p<0.001). However, time from admission to CT head imaging (p=0.003) and the likelihood of not being transferred to a center with acute neurosurgical care facilities (p<0.001) increased with increasing age, too. Further, there was a significant trend for the most senior grade of doctor to review more younger patients and for only the most junior grade of doctor to review more older patients (both, p<0.001). To conclude, our data suggest differences in management practice may contribute to the observed differences in mortality between younger and older patients suffering brain contusions.

The UKCRR will be an important pillar in the ongoing efforts to optimise the outcomes of patients undergoing cranioplasty.